Disclosed are compositions and methods comprising a novel tumor suppressor gene, designated NOEY2, that is expressed in normal ovarian and breast surface epithelial cells but consistently absent or down-regulated in ovarian and breast cancer cells. Disclosed are polynucleotide compositions comprising a NOEY2 gene from mammalian sources, and polypeptides encoded by these nucleic acid sequences. Also disclosed are methods for preparing NOEY2 polypeptides, transformed host cells, and antibodies reactive with NOEY2 polypeptides. In certain embodiments, the invention describes methods for diagnosing and treating cancers, as well as methods for identifying NOEY2-related polynucleotide and polypeptide compositions.